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Transcriptional and Distributional Profiling of Microglia in Retinal Angiomatous Proliferation
Macular neovascularization type 3, formerly known as retinal angiomatous proliferation (RAP), is a hallmark of age-related macular degeneration and is associated with an accumulation of myeloid cells, such as microglia (MG) and infiltrating blood-derived macrophages (MAC). However, the contribution...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998238/ https://www.ncbi.nlm.nih.gov/pubmed/35408803 http://dx.doi.org/10.3390/ijms23073443 |
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author | Schlecht, Anja Wolf, Julian Boneva, Stefaniya Prinz, Gabriele Braunger, Barbara M. Wieghofer, Peter Agostini, Hansjürgen Schlunck, Günther Lange, Clemens |
author_facet | Schlecht, Anja Wolf, Julian Boneva, Stefaniya Prinz, Gabriele Braunger, Barbara M. Wieghofer, Peter Agostini, Hansjürgen Schlunck, Günther Lange, Clemens |
author_sort | Schlecht, Anja |
collection | PubMed |
description | Macular neovascularization type 3, formerly known as retinal angiomatous proliferation (RAP), is a hallmark of age-related macular degeneration and is associated with an accumulation of myeloid cells, such as microglia (MG) and infiltrating blood-derived macrophages (MAC). However, the contribution of MG and MAC to the myeloid cell pool at RAP sites and their exact functions remain unknown. In this study, we combined a microglia-specific reporter mouse line with a mouse model for RAP to identify the contribution of MG and MAC to myeloid cell accumulation at RAP and determined the transcriptional profile of MG using RNA sequencing. We found that MG are the most abundant myeloid cell population around RAP, whereas MAC are rarely, if ever, associated with late stages of RAP. RNA sequencing of RAP-associated MG showed that differentially expressed genes mainly contribute to immune-associated processes, including chemotaxis and migration in early RAP and proliferative capacity in late RAP, which was confirmed by immunohistochemistry. Interestingly, MG upregulated only a few angiomodulatory factors, suggesting a rather low angiogenic potential. In summary, we showed that MG are the dominant myeloid cell population at RAP sites. Moreover, MG significantly altered their transcriptional profile during RAP formation, activating immune-associated processes and exhibiting enhanced proliferation, however, without showing substantial upregulation of angiomodulatory factors. |
format | Online Article Text |
id | pubmed-8998238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89982382022-04-12 Transcriptional and Distributional Profiling of Microglia in Retinal Angiomatous Proliferation Schlecht, Anja Wolf, Julian Boneva, Stefaniya Prinz, Gabriele Braunger, Barbara M. Wieghofer, Peter Agostini, Hansjürgen Schlunck, Günther Lange, Clemens Int J Mol Sci Article Macular neovascularization type 3, formerly known as retinal angiomatous proliferation (RAP), is a hallmark of age-related macular degeneration and is associated with an accumulation of myeloid cells, such as microglia (MG) and infiltrating blood-derived macrophages (MAC). However, the contribution of MG and MAC to the myeloid cell pool at RAP sites and their exact functions remain unknown. In this study, we combined a microglia-specific reporter mouse line with a mouse model for RAP to identify the contribution of MG and MAC to myeloid cell accumulation at RAP and determined the transcriptional profile of MG using RNA sequencing. We found that MG are the most abundant myeloid cell population around RAP, whereas MAC are rarely, if ever, associated with late stages of RAP. RNA sequencing of RAP-associated MG showed that differentially expressed genes mainly contribute to immune-associated processes, including chemotaxis and migration in early RAP and proliferative capacity in late RAP, which was confirmed by immunohistochemistry. Interestingly, MG upregulated only a few angiomodulatory factors, suggesting a rather low angiogenic potential. In summary, we showed that MG are the dominant myeloid cell population at RAP sites. Moreover, MG significantly altered their transcriptional profile during RAP formation, activating immune-associated processes and exhibiting enhanced proliferation, however, without showing substantial upregulation of angiomodulatory factors. MDPI 2022-03-22 /pmc/articles/PMC8998238/ /pubmed/35408803 http://dx.doi.org/10.3390/ijms23073443 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Schlecht, Anja Wolf, Julian Boneva, Stefaniya Prinz, Gabriele Braunger, Barbara M. Wieghofer, Peter Agostini, Hansjürgen Schlunck, Günther Lange, Clemens Transcriptional and Distributional Profiling of Microglia in Retinal Angiomatous Proliferation |
title | Transcriptional and Distributional Profiling of Microglia in Retinal Angiomatous Proliferation |
title_full | Transcriptional and Distributional Profiling of Microglia in Retinal Angiomatous Proliferation |
title_fullStr | Transcriptional and Distributional Profiling of Microglia in Retinal Angiomatous Proliferation |
title_full_unstemmed | Transcriptional and Distributional Profiling of Microglia in Retinal Angiomatous Proliferation |
title_short | Transcriptional and Distributional Profiling of Microglia in Retinal Angiomatous Proliferation |
title_sort | transcriptional and distributional profiling of microglia in retinal angiomatous proliferation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998238/ https://www.ncbi.nlm.nih.gov/pubmed/35408803 http://dx.doi.org/10.3390/ijms23073443 |
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